Logistically, this fully integrated portal represents an advancement over previous attempts at coordinated reviews, such as the voluntary harmonization procedure (VHP). However, while the VHP was optional, allowing Sponsors to make filing decisions based on the clinical trial’s scale across regions, using CTIS will soon be a mandatory requirement.
Changes Coming in January of 2023
Starting in January of 2023, the older Clinical Trials Directive approach to filing will no longer be an option for new clinical trials. Many professionals experienced with CTAs will face an unfamiliar portal and workstream.
In addition to the technical and IT challenges inherent in setting up and establishing permissions and roles within a portal while juggling clinical trials startup activities, Sponsors must be forward-thinking in their preparations for the public accessibility of submission components uploaded to the portal.
Integrated working models involving close coordination between Regulatory Strategy, Regulatory Operations, Medical Writing, and Transparency will be critical in preventing delays and unanticipated consequences within the new system.
Embracing the Change
2023 will be a very important year for clinical trial applications submitted in European Union. Although the regulation went into effect on January 31, 2022, there has been a slow but steady uptick in the number of clinical trials submitted in CTIS. Sponsors must be on time, as all new clinical trials must be submitted in CTIS beginning January 31, 2023.
CTR is a harmonized dossier in a centralized system with standardized competitive timelines for all parties. It allows for a smoother work-sharing arrangement between Reporting Member State (RMS) and other concerned member states (MSCs), which culminates in a single decision for the trial. The process is fully electronic with a primary objective of increased transparency in the publication and sharing of clinical trial data and documents.
The first year of CTR implementation has been the year of learnings and adjustments for Sponsors and regulators such as National Competent Authorities (NCAs) and Ethics Committees (ECs). EMA continues to enhance and develop operations and IT for training and support with CTIS.
If you still need to prepare, you must develop robust processes, procedures, training, and documentation of all CTIS-related activities within the organization.
Sponsors should deploy a team of experts from all functional lines to be part of their internal CTIS steering committee and update processes as they adjust to the regulatory, compliance, and transparent environment of CTIS and CTR.
The Dream Team
Integration between Regulatory, Medical Writing, and Transparency teams will be essential for clinical trial applications in CTIS.
While working or transitioning to new submission portals is not uncommon for regulatory teams, CTIS is a next-level portal with a broader purpose in actualizing the EU CTR, necessitating an all-hands-on-deck approach.
Attention to detail and documentation are necessary when setting up user access as there are 18 specified user roles in the system, each with different levels of editing, viewing, and submission accesses.
Experienced Regulatory Operations teams with strong knowledge of CTR and CTIS (preferably with hands on experience with the CTIS Sandbox) are required to ensure proper naming conventions, version controls, and awareness of best practices for structured data and documents within CTIS fields.
Transparency Is Built into Every Step of CTR
With increased transparency comes higher consequences for mistakes. For example, accidentally uploading a quality document that is part of Request For Information (RFI) responses to incorrect sections could inadvertently lead to releasing commercially confidential information (CCI).
Anonymizing the data can be easier if clinical trial documents are authored with disclosure in mind. Sponsors can prepare for this by:
- developing and implementing lead-authored templates
- avoiding the inclusion of personal and confidential data when possible (for example: cross-referencing to other sections/documents that are not subject to publication)
- using consistent Personal Protected Data (PPD) terminology
- early identification of CCI information that can be harmonized across all sections or documents
Communication and good process will be crucial to document handoffs from authoring to translation to anonymization (and vice-versa) and ultimately through submission in CTIS. Communication and process continue after submission and will also be essential during the monitoring stages. With no automated notifications in CTIS, there is a need for additional resources to monitor system alerts, notices, RFIs, etc.
Functional teams must be brought together to develop a governance strategy to prevent delays or lapses in the application. During this time, regulators, sponsors, and CROs may continue to change processes, so it’s time to roll up your sleeves, buckle up, and embrace the ride.
By: Swathi Pandhiti, Associate Director of Regulatory Operations